ESMO Asia 2025 | TROPION-Breast02: first-line datopotamab deruxtecan in metastatic TNBC

Yes, so I had an opportunity to discuss TROPION-Breast02 from Asian perspective during ESMO Asia this year. As TROPION-Breast02 Asian substance is not available, that was just presented in ESMO in October, I just analyzed the existing data to discuss whether there are differences in efficacy and toxicity based on the ethnicity-racial disparity and discussed in this context. As you know, the TROPION-Breast02 is a randomized phase 3 open-label global trial evaluating the data DXD versus invasive choice chemotherapy as first-line metastatic triple-negative breast cancer in patients for whom PD-1 or PD-L1 immunotherapy was not an option. A dual primary endpoint was met. That was reported as small. By Becker and over survival. Looking at the demographic, 47% is Asian. So looking at the subgroup analysis, PFS and overall survival subgroup analysis, better hazard ratio was observed in Asian as compared to non-Asian. So this finding raises another question. Are there differences in efficacy by ethnicity or race? How this feels in the evolving ADC landscapes? Looking at another ACE-12-2 ADC, Ascent-0-3, that Ascent-4, Asian population just 20%. Ascent-0-3, Ascent-0-4 did not include Asian sub-global analysis data in clinical design. Other trials, Ascent-0-3, Ascent-0-4 did not include Asian sub-global analysis data in clinical design. Other trials, Ascent-0-3, Ascent-0-4 did not include Asian sub-global analysis data in clinical design. Other trials, the ASCENT trial in metastatic setting, second line or later line, 4% Asian. And EVO-132-001 is all Asian cohort, but there’s no difference. TROP-PEN-02, Asian population, better efficacy, but another TRO and Govitigan, similar efficacy. What about the TDXD? The TDXD, Destiny 0 for the Asian population is 40%. The hazard ratio seems to be better. PFS has a ratio 0.38 versus 0.50 in overall population. But this is your study. The Asian population is increased up to 59%. But hazard ratio is almost similar. So Asian population do not guarantee increase of the favorable hazard ratio. So we should be cautious to interpret the research based on the ethnicity. But previous data, there is a racial disparity in chemo-sensitive affected survival in early TMBC. That was a reported JAMA network open to 2023 journal. And also the Keynote 355 and Keynote 522 subgroup analysis that immunotherapy benefit is better in Asian TMBC population. So why is that so? The Asian investigators explore that reason. So multiomic profiling in Asian breast cancer demonstrates the higher PD-L1 and lower TZF beta and immune score is higher in Asian population. That may be related to better efficacy in Asian population when the immune checkpoint is administered. And also molecular characteristics are somewhat different. So higher prevalence of luminal androgen receptor subtype and the pixelation mutation is higher in Asian population than as compared with TCGA. This could be the efficacy difference according to ethnicity. And trap 2 expression, the high versus low proportion is almost similar. That was similar in a center trial versus OptiTROP-Breast02 study, which is done in Chinese group. As you know, different ADC has unique and common AEs. So the question here is, are there differences in safety, toxicity profile by ethnicity? TROPION BLAST-02, the key treatment related AEs, stomatitis and neutropia, and nausea. In contrast, Center 0-3, the sacituzumab govitecan, and the higher neutropenia, diarrhea, was observed. That underscored that the toxicity profile could differ across the ADC. That is a matter for selection. So toxicity may vary as a mystery in that high incidence of a TDX-ILD was observed in Japanese patients. And also there’s a UGT1 variation that may contribute to AE differences. So when TROP2, TDXD, Tropion BRAS-02 was reported, a SENT-03 study was also reported in ESMO. So key practical issue in this setting is how to choose between two different ADCs. So similar efficacy, but toxicity profile is different. The admission schedule is different. Patient’s preference is also important. What regimen we choose. So my top topic lecture was that a discussion was summarized like this. Dato-DXd significantly improved the survival-enforcer line TMBC who are not candidates for PD-1 inhibitor. At least the TROP-2 data DXD, the benefit is consistent in Asian population and toxicity profile may differ, but safety consideration will be important in treatment selection. That was what I discussed in the ESMO Asia highlight session.